discussion on this research center, Sanders-Brown Research Center onAging. If you would maybe start from the beginning there again--

MARKESBERY: Okay.

SMOOT: --and just kind of bring it through to the present, what this

institution is all about, how it got started, uh, the origins anddevelopment of this institution over the years that you have beenassociated with it.

MARKESBERY: The historical perspective, you want all of that?

SMOOT: Yes sir I do, if you please.

MARKESBERY: Okay. Now I have to be consistent because you had some of

this before. (laughs) There were some aging activities, uh, in theUniversity of Kentucky in the seventies but in 1972 or '73 the John Y.and Eleanor Brown Foundation gave a million dollars to the universityfor the purpose of building a building to support the biologic researchof aging. And, uh, the state legislature matched that with another1:00million dollars and then I think there was a significant amount ofmoney from the university to put into this to build a building, whichculminated in the present Sanders-Brown Building, which was dedicatedin the fall of 1979. It has about thirteen laboratories, they're wellequipped, it has a barrier animal facility on the fourth floor; uh,it has a lot of support, uh, space for our secretary office, office,uh, space that is, and a, uh, conference room and library combined;so it's a very nice building for that purpose. It was dedicated, uh,uh, in the fall and the, uh, charge at that point was to get something2:00started. And I took the job as director in the fall of 1979, withthe hope of getting biologic age-, research in aging, uh, underway.We, uh--with funds from the dean of the College of Medicine had,uh, starter money for equipment and we had, uh, lines for about threefaculty members at that point. Mind you we had a number of, a largernumber of laboratories, we have like, I think there are thirteenlaboratories, let me count ----------(??) write it down--(pause)--eleven, I think that's right, twelve or thirteen laboratories. Anyway,uh, then we hired, uh, some faculty members, uh, and being a center,you don't really have, you don't have the status of a department,3:00so individuals that you hire have to be in a different department.Uh, and so we hired people in the department of biochemistry and inanatomy. Uh, in addition, we brought in a number of people in thebuilding that were interested in nervous system. Some from neurologyand I happen to be from neurology, but that's not the full reason,you try to develop then, uh, aging in the nervous system, as our majorprospective. And to do that we've had to unite people from--

UNIDENTIFIED WOMAN: Dr. Markesbery?

MARKESBERY: Yes.

UNIDENTIFIED WOMAN: Dr. Cushell (??) is on line one.

MARKESBERY: I'm sorry, I'm busy, uh, could you just take a message for

me?

UNIDENTIFIED WOMAN: Oh, okay. Will do.

MARKESBERY: Um, anyway, we had to reach across to people in a lot of

different departments. And as a matter of fact, in different parts ofthe university on the Lexington campus as well. So we are very pleasedto have amalgamate of people from the un-, Lexington campus department4:00of chemistry and department of psychology with people from the MedicalCenter, departments of anatomy, biochemistry, physiology, pathology,neurology, just to name a few. Uh, a number of different departmentsaided to the program here, say aging in the nervous system. And ourfirst bit of luck came when we got a training grant to train pre andpostdoctoral students in 1981 or '82. Uh, and that was about a halfmillion dollar grant, that allowed us to recruit postdocs and graduatestudents and has been very helpful to us. Then, um, we were veryfortunate to tie together a group of people and get what is called aprogram project grant in Alzheimer's disease, and which again was a, Ithink a million three or a million four or five, uh, thousand dollars,five hundred thousand dollars to, uh, study the causes of Alzheimer'sdisease. And then superimposed on that was a anoth-, another grant5:00which became a, developed a center grant proposal and became one of theten centers in Alzheimer's disease. And the reason we were able to getthat I think was we had the program project grant as an underpinningfor that, plus we had a very broad program in Alzheimer's disease.So that established us as one of the ten, um, I'd say leading centersin the country studying Alzheimer's disease, both from the clinicalstandpoint and research standpoint, and from a service and educationalstandpoint. In addition, we joined forces with Dr. Ted Kotchen inthe Department of Medicine and, uh, through his initiative we havea, um, about a million pl-, a million plus grant from NIH to studysystolic hypertension in the elderly. So the program we developedand the end-point of that is stroke and heart disease, so the major6:00focus we have is how the brain ages and what happens to it over, overthe years. And it is a very timely program to develop because of themajor push now with Alzheimer's disease, it just sort of carried usalong with it. In addition, the programs that have developed here areexercise physiology, that is exercising the elderly, uh, and how it canalter your physiologic response, uh, and a program in how the immunesystem declines with normal, with aging, as a normal cogent (??) ofaging, I should say, and how this potentially relates to the diseasesof the elderly. And in addition, the program here has, uh, taken inall the aging studies going on in the whole university. As the--that7:00is to say, all aging activities of any type are carried on under theMultidisciplinary Center for Gerontology, which I think is, I think thename of that is going to be changed relatively soon to the University ofKentucky Center on Aging or Aging Center. I'm just about to have themget rid of Multidisciplinary, uh, Center of Gerontology and the Centerof Ground Research here on Aging, which is a headache for anybody totry and say, much less remember. So the Council on Aging, which is aDonovan scholar program is a, under the social and behavioral sciences,um, are also here, as well as all those Medical Center studies, uh, inthe biologic aspect of aging, so the program has developed and, uh, wehave had a little luck and we've had a very good support system fromthe administration of the Medical Center and the university in general,which is a lot of, it's developed, you know, well.8:00

SMOOT: What is different about what this center is doing versus other

centers studying these various, uh, problems across the country?

MARKESBERY: You mean others that are Alzheimer's disease centers or

other centers, aging centers?

SMOOT: Aging centers, generally. Of course, Alzheimer's is one specific

then to deal with, uh--

MARKESBERY: Right. Well, the difference in this aging center and I'm

not exactly sure how it got, I guess the money called the tune, that'show it got its start, but this center developed first the researchbase. Now other centers have developed the social and behavioralscience descriptive aspect of aging first, or the clinical care andgeriatrics part of it. Well, what has happened here, we developed the,the biologic research aspect first and then the social and behavioralaspect and then the clinical and geriatrics part, which is under-,underway now, it's d-, it's undergoing development and has a major9:00push from the College of Medicine. The Medical Center, in general,has developed, uh, a teaching program and a clinical care program forthe elderly. And the importance of all of that is, there's severalimportant factors. It's very difficult to get a physician to go intoa nursing home in this day and age. I mean our nursing home careis abysmal, not only in Kentucky, but in this country. In CentralKentucky we do as well as any place, I think, and it is still not verygood. We really have to upgrade the care of our elderly and, uh, wehave to get physicians interested and to do that you have to, you can'tgo to a fifty or sixty year old physician and, and reacquaint him withhow you practice medicine, he is already fixed in his routine, hisbeliefs. What you have to do, you have to influence medical studentsand house officers. So our plan is to get more geriatrics into the10:00medical school curriculum and, uh, to have a rotation for medicalstudents involved with the clinical side of this, this program. Andin addition, to establish links with, uh, nursing homes and developteaching nursing homes that will have the goal as strong as you cangive, uh, ideal optimum care with cost containment and, and reallyestablish these, this nursing home as we are trying to develop theteaching nursing home, as one that is, uh, an exemplary standard ofexcellence for teaching not only physicians, but nurses and pharmacistsand all your health care professionals. Anyway, so this center hasdeveloped a little differently than most aging centers. And I don'tknow whether has given us a leg up or whether it is good, but so farwe've had, we've had pretty good luck, and I think it's probably an11:00ideal way to do it. We get some other folks coming in from outsidethat say it is a pretty good way of doing it. Establishing yourbuilding and your basic science research program and then adding on tothat the social and behavioral and the clinical aspects of.

SMOOT: Demographics would seem to dictate that a lot of people would be

going into care for the elderly, uh, considering that the population isgenerally aging, you have a baby boom generation that just turned fortyand in a few more years, of course, you're going to have those peopleentering into their sixties and so on, and hopefully well beyond thatbecause of the advances made in longevity and these types of things.Uh, what is keeping more people from going into, uh, care for theelderly? It is not as lucrative as some of the other areas?

MARKESBERY: It's partially that. Uh, it is not as romantic and dramatic

and as exciting. There are a lot of chronic diseases there that youcan't cure, you know we, we all go into medicine thinking we are goingto cure man's ills, and, uh, it's just not as exciting to get chronic12:00diseases that you, and, uh, people that, uh, are older and you probablydon't relate to as well. And, uh, who have multiple diseases in most,uh, people over sixty-five or seventy on; multiple different medicationsand multiple problems associated with aging. So it's just the lack ofexcitement and I, I, it's a little less lucrative, I suspect, but, uh,not much more well, not much less lucrative than other, other fields.I, I think it's more the view that you are caring for older peoplein a nursing home and that's all there is to it, which it really notwhat geriatrics is. It's a continuing of care from the home to thehospital to the chronic care facility and back home, hopefully. Andit encompasses physical medicine and rehabilitation and preventive13:00medicine just as well as any other; and I think we need to become moreaware of that in geriatrics. And I think you are going to see a, adevelopment of more aging programs and I think eventually we'll findthat--you'll find, uh, more physicians going into studying, uh, theproblems of the elderly and caring from them a little bit better; butit's really not happening right now, and it would probably have to belegislated on us before we really get carefully serious about it.

SMOOT: Um-hm. You mentioned earlier that in fact the state, and it has,

there's been general expose as being abysmal, that is to say nursinghome care throughout the United States.

MARKESBERY: Um-hm.

SMOOT: What do you think may be the major causes for this? It is because

of the, uh, people that go into geriatric care? Is it because of the,uh, social, uh, factors involved with the, dealing with across thegenerations? Or is it just a broad range of things that you would sight14:00as being the major causes for, uh, problems in that particular area?

MARKESBERY: That's really a very good question, because you know you

look at it historically, most of our grandparents, uh, and theirgrandparents were cared for in the home. We didn't have institutionslike we have now. Uh, there were a few state institutions where ifpeople became severely demented or weren't able to be cared for intheir home, they were placed in state institutions. But for the mostpart, families pulled up their bootstraps and cared for their lovedones in their home. Now this had some--adds historical perspectiveand I think of an interesting thing that happened to me one time. Imentioned to you, we had a joint meeting with, uh, sort of Russianphysicians and scientists that came over and for an exchange, theycame out of university. I asked them the question, through multipleinterpreters, "What were their nursing homes like?" And they gave mea very flat answer, "We don't have much more nursing homes." "Well,15:00who cares for your, your chronic care elderly patients?" Said, "Well,they're cared for in their homes or loved ones." "Well, what if theycan't do that?" "Well, they're cared for by the next door neighbor.""Well, what if they can't do that?" "Well, they are cared for bysomeone in that community and if not in that community, then anadjoining community." And they made it sound, now you have to, to putthis in context; it was through multiple interpreters in the Russians,like you have nothing but good news. And certainly have great respectfor their elderly and, uh, perhaps that may be a very, very importantfactor. Anyway, they, they seemed to truly have more respect and moreinterest in caring for their elderly. And our, uh, yuppie generationand our present, uh, younger generations aren't terribly interested incaring for their loved ones in their own home; so now we have lots ofnursing homes developing. And it's a proper motive in most instances16:00and it's not done with the loving care that you get in a home,therefore, it's done, it's done, and the care is ten-, given by peoplewho are there because they are working an eight-hour shift, and theyare there because they are making dollars to put food on their table;and they really don't have the missionary zeal and the deep-rootedinterest in giving the kind of care that's really needed. So there'sthat factor, factor of, of not being very exciting for physicians;and you end up then with, uh, less than ideal care because there isno commitment on the part of American medicine or in those reallyrunning the nursing home to really give the best of care. Plus you aredealing with diseases that we can't, there's no cure in many instances.17:00Um, osteoarthritis, for an example, incontinence, variety of causes,dementing diseases, uh, severe heart disease, cancer, uh, these are thethings that are in nursing homes and, uh, they are harder to do muchwith and we are just not giving the best care, but we can't go on likewe are. We are really going to have to improve our care in that. Idon't think I really can answer your question well. There are a lot offactors that go into this, uh, something has to be done to improve it.

SMOOT: Do you see something along the lines of, of trying to educate

people into the importance of trying to take care of their elderlywithin the home, or perhaps within, at least within the communityin which they are from and then maybe some kind of like outpatientarrangement with them to get the specialized treatment that theyare going to need. Because after all, you can't get those kind oftreatments outside of a established medical facility.18:00

MARKESBERY: You are absolutely right. Uh, in the background for that,

there are, there is a great push by our administration that is ourstate and federal administrators, to keep people in the home. And, uh,more dollars are being spent trying to determine ways that people cancare for them in their home and not in nursing homes, because nursinghomes are eating up large segment of our health care budget. Butyour question is a very interesting one in that our center has justreceived from the state legislature through the center of excellence,we were one of the ----------(??) of excellence at university, todeliver the programs that were funded in our center of excellence,are to give, to go to the outreach areas of the state of Kentucky, ina number of different settings. It's a team of, a health care team19:00of physicians in both the workers and nurses; and improve the care ofdemented individuals, primarily those with Alzheimer's disease, butany dementing disease. But also in the Department of Medicine, to carefor individuals, to educate, uh, caregivers on the how to improve thecare of their loved ones in the home; and I think it is very important.So it's a role that the major medical centers are going to have take.Being a small state like this with a large rural segment, we haveto, uh, we are in an ideal position to establish programs that couldbe national models for this, as a matter of fact, on how to do goodoutreach care and keep people in their homes as long as possible andkeep them out of nursing homes. But I truly believe, in the--I'll getmyself in hot water putting this on tape, I'm sure--but I truly believethat the care in the home by someone who loves you, um, with, uh, aloving physician as well, and a caring physician, is much better than20:00you will get in a nursing home. Because there are people there thatcare about you twenty-four hours a day and in a nursing home you getthree eight-hour shifts. You're there because, they, they may be well-intentioned and good-hearted, but they are still not your relatives and,don't, you know, not a husband or a wife or a son or a daughter, andwill not just give the intimate care that someone would give if theyare a loved one. So I think we ought to do everything we can to keeppeople in their home. There is a limit on what families can do andwhat caregivers can stand, and they eventually will in many instances,uh, give up, put up their hands, I can't give this person anymore andat that point then we need chronic care facilities. But that system ofchronic medical care system has improved considerably and that is oneof the things we would like to help do here at this center.

SMOOT: Let me draw back on another thing that you mentioned in

21:00describing the center. Uh, you mentioned that you had animal, animalshere for experimentation.

MARKESBERY: Um-hm.

SMOOT: Is that correct? Have you ever had any problems with that in

terms of outside factors like the, uh, Society for the Prevention ofCruelty to Animals--

MARKESBERY: Um-hm.

SMOOT: --or any of these people that have, uh, raised questions or

complaints about your use of animals for experimental purposes?

MARKESBERY: We haven't had direct complaints to us that I am aware of at

this--up until now. Uh, there is quite an outcry from the National ----------(??) group, but, um, using experimental animals is not correct.We use rats and people are less likely to be concerned about the ratthan they are with a cat and a dog and a monkey, and, uh, so in a sensethere is not as many rat lovers out there as there are dog, cat andmonkey lovers and I can, can identify that and understand that. So,22:00but use primarily using rats; there are a few guinea pigs, uh, and, uh,but primarily rats. Very interesting that an old rat will cost, uh,I guess now about a hundred and fifty dollars. You think about a ratitself costing a hundred and fifty dollars is quite amazing. Um.

SMOOT: Can't use some of the, uh, local rats that are running around

here? (laughs)

MARKESBERY: Well, it's kind of hard to, kind of hard to find. These are

rats that have been raised under lovely controlled conditions.

SMOOT: Um-hm.

MARKESBERY: One of the things we are doing here is, uh, our barrier

animal facility allows us to raise animals under completely controlledconditions. And, uh, we can raise a rat from day one through, uh,twenty-four to thirty months here and have our own colonies, and knowthe exact environment in which they have been raised and the humiditylevel, the noise level, the temperature level, what they've eaten,what their bacterial flora is throughout their life. Therefore,you know the life history of that animal and have a better chance23:00of understanding his response to normal aging, which is very, veryimportant. The National Institute of Aging established a policy that,that supported and, uh, pushed for individual medical centers to havebarrier facilities so that true aging studies could be done, um, withthe right kind of animals, and, uh, we were fortunate enough to havefunding for that when the place opened and it's taken a long time, butwe now have our barrier animals, um.

SMOOT: I know that other parts of the Medical Center uses cadavers for

experimental purposes. Does this center use them as well?

MARKESBERY: No, we don't. Don't have any.

SMOOT: Don't have any use for that sort of experimentation?

MARKESBERY: No, we do, we get brains from all over the country as a part

of a national autopsy network and as part of our Alzheimer's diseaseresearch center, but it, it's the brain only.

MARKESBERY: Well, obviously, the family has to give their permission and

we send them a report on what, uh, we find, uh, in their loved one'sbrain. And, uh, then we can utilize that part of the brain that-- youtake part of it and freeze it and part of it -------------(??)--and weutilize that for all our studies, and that's, that's inherent in thepermission that we get from the family. And it's very interesting thatmost families of loved ones with Alzheimer's disease want an autopsyand want to prove that's what it is, because that's the only way in theworld to prove that diagnosis. And, two, to try and do something aboutthis disease by, uh, offering the brain for research uh, it's beena very supportive system of families and it's been done through verycareful education of these families. It, it's very difficult to go outand say we, you know, "We want to take care of your loved one," and we25:00eventually we'll ask, may I ask you--we don't do this ahead of time--weask, ask them for autopsies. Uh, and you know some people have verystrong feelings about autopsies. Obviously, it is a very sensitiveissue and we just ask and if they don't want it, that's just fine. Buta number of families--I think Dr. Wilson will tell you that--there areover forty or so now that have pre-arranged for autopsies to be doneon their loved ones while they are still alive. So this is a, a nice,a nice feature of the eighties where people are having an, an informedview of what the disease is about and how in the world we can ever getthrough a position where we can understand it, by allowing us to tellyou that the only species that develops it is man. It doesn't happenin lower animals, you can't see the disease in animals at all, andthere's no experimental model for it; therefore, you have to study itin human beings. So very, very, very helpful to us to be able to bean autopsy center, one of the three autopsy centers in the country, as26:00well as, uh, have our own ----------(??) autopsy network here in theMedical Center.

SMOOT: What's the method of disposal of these organs once they have,

once the experimentation has been terminated?

MARKESBERY: They are cremated. They are cremated.

SMOOT: Um, I heard recently, I suppose it was on the news or perhaps

it was in the newspaper. I really can't recall, that, uh, they hadsome sort of significant breakthrough in, uh, with the diagnosis ofAlzheimer's or is this perhaps something that has come out a little bittoo soon. You, you recall?

MARKESBERY: No ----------(??).

SMOOT: Could you tell me a little bit about that, uh?

MARKESBERY: Sure. One of the major problems that we had in Alzheimer's

disease is about once every two months the National Enquirer gets ahold of some piece of research and sensationalizes it. The last onewas a protein that's in the brain of patients with Alzheimer's disease,called alz-, A-l-z50, Alz50, and it was done by a very good laboratory27:00at Albert Einstein College of Medicine in New York, a man named PeterDavies, that I know. And, uh, it was overplayed in the, in the pressas a magic breakthrough and what happens every time this happens,uh, something comes up, the families all say, gee, here, here's thebig breakthrough, through we're looking for. In point of fact, itreally isn't. It's a nice piece of research that was in Science andit may help considerably down the road, but it doesn't give rise toa diagnostic laboratory test at all, and it hasn't improved our, ourposition in terms of treatment or anything else at that point. Ithas some promise in the future, but it just got played way out ofproportion. It was on nightly, national nightly news--

and the press and the media in general just sitting there waiting fora big breakthrough. It's probably not going to come for a long time.Small little steps like this one is going to add to our knowledge.I was c-, I was on a NIH study section, uh, up until the last year,and one of the study section meetings--which we worked our heads offfor three days in Washington reviewing a grant. Um, I got a call fromthe associate director of a NINCDS, which is the National Institutefor Neurologic Disease and one, and there was a new drug that cameout potentially, uh, curing Alzheimer's disease. Would I get busyand learn everything I could about this and, uh, perhaps be ready to29:00testify before a congressional committee. And, uh, the bottom linewas that this wasn't any more of a breakthrough than anything else,but someone had treated five patients and said they had improve-,or, you know, five patients said they improved. Something got into,uh, I think it was Time or Newsweek not too long ago, as a majorbreakthrough, where they had studied five patients by putting ----------(??) down the brain, drifting in, uh, an old-fashioned drug calleduracolene (??) in the brain for, uh, a longer period of time, and thefamilies said they improved, although neuro site testing said they didnot. This got into, into the lay press and was heralded as a new wayof treating Alzheimer's disease. And we have to guard against thosethings, they are very, gets the hope of the families up falsely and,uh, then they come crashing down when they find out there is reallynot a cure and there's really nothing new to diagnosis the disease yetand we have to very patient. So your question is a very good one, butwe're-- those sort of things do happen--but, um, those of us who are30:00in the ten centers have to fend off the questions of the, of the caregiving families and the early patients and when you know, this whatwe've been waiting for? When in fact it isn't, so you have to give badnews all the time.

SMOOT: Um-hm. How much information does someone in your position, doing

research on something specific like Alzheimer's disease, you comparethe areas of research such as, uh, something that springs to mind tome would be genetic research or any neurological research that might begoing on and would somehow relate to, uh, your own research?

MARKESBERY: Well, what, what you try and do in this business is to find

out what new probes are being, new research tools are being used inwhatever field and immunology has developed very rapidly. It is sortof a field of the eighties. Molecular genetics is going to be thefield of the late eighties and the nineties, I think perhaps I may havemisstated, maybe immunology is the field of the seventies and molecular31:00genetics is a field of the eighties, but just developing now; so itshould develop even into the nineties. But what you try and do is usethose techniques and apply them to the disease you are studying. Soyou do try and keep up with other areas and hire good people in thoseareas if you can to try and enhance your program. And to have themapply their tools or in learning what new tools you can use from alliedfields and biochemistry and mo-, um, molecular biology and genetics andthings like that, and apply them to your field so it is important tokeep up. If you go to the meetings you will see that in the area ofAlzheimer's disease that very specific new molecular genetic probes arebeing used to study Alzheimer's disease. It is about somewhere in therange of 20 to perhaps 30 and maybe even more percent of Alzheimer's32:00disease that is inherited that we know of and you need to study thatgroup of patients intensely as sort of a window into the diseaseoverall. So, you comment about genetics and immunology is really avery good one, especially about molecular genetics.

SMOOT: Let me ask you something similar, along similar lines. Uh,

perhaps this is something that is a bit faddish but springing forthfrom the youth cult that we seem, uh, to, uh, keep going very strongin the United States, but, uh, for a long time you'd hear people, notnecessarily in the medical professions, but futurist and these typesof people talking about the benefits of exercise, benefits of nutritionand taking mega doses of, uh, vitamins and so forth to keep you younglonger, make you stronger, increase your longevity, et cetera. Haveyou been doing any research along these lines, uh?

MARKESBERY: No, we really haven't. There--the, uh, I guess you'd look

upon the research we are doing here as trying to improve the quality33:00of life to the other end of the spectrum, rather than extending thelife to the other end of the spectrum. So we really haven't done that.The exercise physiology person here, Dan Richardson, has just gottena grant to study, uh, how the, uh, capillaries have changed with agingand how they change with exercise in the elderly; which will give somegood basic information, but we're not doing any directly with, uh,nutrition or exercise. In the, should say, uh, in the Don-, in theDonovan program there are exercise fitness programs for, for them,which are utilized, uh, considerably by the people in the Donovanprogram. And I have a feeling we should be doing more with exercise,you probably saw an article in the last month, or maybe the last coupleof weeks, that shows that exercise can increase the, uh, mobility and34:00perhaps the length of life, uh, if you exercise regularly. And weprobably should be doing more with that, but we're not. It's a goodarea to expand into.

SMOOT: Is this something that you would need direction from the, uh,

federal or state governments, uh, in order to do or?

MARKESBERY: No, I think it can be local internal decision if we wanted

to develop in that direction and probably is one that we should, butour walls are sort of bulging right now, we don't have enough space foreveryone. So we're, you know, we're, we're a little bit hesitant aboutadding new programs until--we don't have the space ----------(??). Weare trying to make the ones we have, uh, sort, of, uh, standards ofexcellence and do our best to make them, uh, productive.

SMOOT: Well, my understanding of applied research is, is you are given

a specific task, okay, versus just generally expanding knowledge insomething like basic research where you are really given a free handto do whatever sorts of research you might want to do within thegeneral framework of the institution versus giving an assignment from agovernment, almost on a contractual basis, to perform, uh, certain, uh,tasks, to, uh, expand knowledge in a specific way, or to, uh, actuallyproduce something specifically.

MARKESBERY: Well, the reason I ask you to clarify that is because, uh,

the research in Alzheimer's disease is, is very specific. We have,we told them what we wanted to do and now they expect us to do it. Inthat sense, we're doing specifically what they have viewed us to do.So in a sense, that's applied, but we have the latitude to freelance36:00within the framework of what we said we'd do, and in that sense it'sbasic. And I think probably if you look at what we do here, it's aboutseventy, thirty basic, uh, seventy, thirty basic to applied that isseventy basic to about thirty applied, okay. Our large grant, uh, insystolic versus chronic hypertension studying systolic hypertensionin the elderly is a contract, uh, that, uh, has us treating patientswith this systolic hypertension with medication and not treating someother people and, uh, applying the outcome of the treatment to see iftreating systolic hypertension really has an effect on stroke or heartdisease, so in a sense, that's, uh, that's pretty applied I think.

SMOOT: Um-hm. Is that the way you would define those, those two terms?

be a need for government intervention, in terms of upgrading, uh, thelevel of health care as provided by nursing home care facilities. Uh,what is your general opinion and perspective on government regulationgenerally in the framework that you work, uh, in, uh, the Center onAging, uh, or I can try to rephrase that a little bit, how would youcharacterize the regulations imposed upon you, and that may be toostrong a word also, but imposed upon you by the government? Do youthink they are adequate? Do you think that they are inadequate? Doyou think there should be more or less government intervention andregulation? What are your general views on that topic?

MARKESBERY: No, I think in what we do here, with, uh, more of an eye

38:00toward research, uh, we are very tightly regulated by, uh, the federalgovernment, because they, they pay us to do this research--

SMOOT: Um-hm.

MARKESBERY: --and I think it is probably appropriate the amount of,

there's a lot of red tape, and you can see my desk is full of papersthat relate to the grants that, that we are dealing with. And it'sa headache in many ways, but it's about the only system that willwork. And I think the regulation of the research component of thefederal spending is done rather well and I think it's not, uh, underregulated, maybe a little over regulated. But, uh, as someone whoworks in that system and who has been a peer reviewer of the workthat goes on there and I'm on that congressional advisory committee.Uh, I think the system works. Now as it relates to clinical care,uh, government control is becoming much more vice-like in making, uh,39:00the paperwork more, making it harder to care for individuals; and I'mnot very excited about that. Although, the other side of the coin iswhen you have to send someone for a CAT scan of the head, that's maybethree to five hundred dollars, I don't believe that anyone should everhave to pay three to five hundred dollars for an X-ray study of theirhead, no matter how fancy it is and how much the machine costs, andI think part of the government control of that sort of thing. So Ihave this ambivalent feeling about it. I, I think we have too manypeople, and again I'm getting myself in hot water, too many peoplemaking too much money out of medicine, and if I could control it,now that I'm, have children and married, I would make the rules suchthat it would be almost a monastic sort of existence. You go intomedicine, you live in the hospital, you care for the people because you40:00are dedicated in doing it, and, uh, you don't have much else to do inyour life. Now, that's very constraining and generally unreasonableand, and sort of a right wing view, but I think we have a situationnow with money--medicine being exploited by folks making too muchmoney and I know I'm overpaid, I'd be the first to admit that. ButI truly believe that we ought to go into medicine for the pure reasonof wanting to take care of sick people. And you have to realize thatit's really an amazing opportunity, because people put their trust inyou, put their lives in your hands, and you have a chance to, to helpthem and we get paid for doing that. I, the system isn't right, itreally isn't right. And I, I think, I, I don't think the governmentcontrol of it will put what I would like to see into it and I thinkthose countries that have government control in medicine have an awful41:00lot of unhappy physicians and I don't have a lot of experience with theEnglish system, but probably not ideal. But I think our system has tobe changed eventually. And, if I could be the architect, there wouldprobably be very few people applying to medical school--(laughs)--Iguess, but there's a guy that really would do what needed to be done,that is dedicate ourselves to taking care of sick people. Because,I think we don't look back enough and say, gee, you know, what was,what were our ideal-, our ideals when we started this? We've becomeflooded by this overwhelming avalanche of information that you haveto learn. You become a little bit burned out early on because thereis so much that you have to do and you have to work so hard, and youstart thinking selfishly. And, uh, once that happens, you lose your,your idealism and I think medicine needs to retain, those in medicine,really need to retain their idealism. And I guess I'm up on a soap-box42:00again, I didn't mean to, that wasn't your question at all, but I thinkit is very important that we maintain our idealism in medicine.

[Pause in recording.]

SMOOT: Well, there are some people that would argue it seems that, uh,

that was the way medicine was, uh, approached by most physicians in theearly days, there was a bit more idealistic tinge to it--

MARKESBERY: Um-hm.

SMOOT: --uh, of course, in the twentieth century and especially

since World War II, there has been a massive growth in the economicopportunities--

MARKESBERY: Right.

SMOOT: --provided to physicians, uh, a real, uh, entrepreneur in

medicine can do very well indeed, and many have done so on a varietyof levels. Uh, you mentioned the English system as, as one model. Ofcourse, now there was Germany and the Scandinavian nations and lots ofother countries, in fact, I would think most other countries have somesort of social system, uh, of course, I could say, socialized system.43:00

MARKESBERY: Right.

SMOOT: Uh, and we have some of that, too. We usually just don't call

it that.

MARKESBERY: That's right.

SMOOT: Uh, and at least on a ----------(??) pay basis, there's nothing

wron-, directly wrong with that, but it is a matter of, uh, how youstructure it, I suppose. And, uh, of course, the organized medicinein the United States has not been overly receptive to that kind ofthinking--

MARKESBERY: Right.

SMOOT: --even though such programs as Medicare and Medicaid has made a

lot of physicians very wealthy.

MARKESBERY: Yeah, and as I, as I think back to my younger days when

a town physician was extremely well respected. And as physiciansincrease their wealth, the curve of their respect in the communitygoes down--(laughs)--it, it seems to me. In spite of all of this, Imay be sounding negative, the medical care given in this country ismuch superior to any other than I know about. And I guess the system44:00works in that regard, but it sure is eating up a mountain of money todo it right now. The technical advances are kind of exciting, we'reable to do things we couldn't do before and, um, make diagnosis wecouldn't make before, so the free enterprise system works in improvingour diagnostic ability and perhaps our treatment ability, but wherewe really get stuck is in diseases such as malignant cancers andAlzheimer's disease and things like that, we can't do, we can't treatthem, we can't prevent them, we can't arrest them, uh, and it's wherewe need to make strides, and that's why you need more people goinginto, into academic medicine to do research. And that's a majorproblem in that we are not getting as many throughout the country, notonly here in Kentucky, but throughout the country good, young, brightminds are not going into the research areas.

other people have mentioned that to me. Well, how long does it take tobecome an academic physician?

MARKESBERY: According to your drive, I, uh, it, you know, it took an

internship in four years after internship, uh, if it took nine yearsof, uh, medical school and specialty training. And that, in all candorprobably had another year or two of fellowship training, but my drivewas such that I could go out and, uh, do research as well as servicework when I finished my training. I'd been much better off if I hadhad a year or two of neurochemistry to top that off, but, uh, it'sa, and it doesn't, you know, it doesn't pay as well as well as if youwere going to go out and go into neurosurgery on Fifth Avenue, I meanyou can make a bundle doing that. So that our system is not rewar-,it's rewarding guys like me, I mean, I'm overpaid as I said, but for46:00the young person starting out, it's not as rewarding financially.But you got to have that burning zeal to want to get involved or bea megalomaniac or have an outrageously large ego to think that you cantackle some of these problems, anyway. And you have to have the rolemodel of someone that sort of struck you early in your training as a,gee, this is, I would like to follow someone like this and, and learnabout how to cure disease or how to approach a disease from a researchstandpoint. I don't think we are doing a very good job of that rightnow. At least that's one excuse for why people are not going intoacademic medicine as much.

SMOOT: What do you see as some of the, of course, I'm asking you now to

go into something very speculative, but what do you see as some of thepossible, uh, benefits to be procured in the future from the research47:00that is being done here? Aside from the direct benefits of, uh,improving care and perhaps even curing Alzheimer's disease. Uh, canyou see other areas that we're goin-, that are going to be benefittingin a major way or perhaps in an indirect important way, uh, from theresearch that is being conducted here?

MARKESBERY: Well, I guess I'll have to be very self-serving to think

we are going to have a major impact on any of the diseases that we arelooking at or anything that we are studying, but since there have beenthousands and probably tens of thousands of people studying cancerfor over thirty years and we're still no further along in that area,probably not even when you think that we're going to have a luckybreak here and find a cause or a cure for any diseases, but we mightadd small little building block increments to the overall effort to48:00understand some diseases or how the body ages. I think that is partof what we are going to do here. The, the dramatic breakthrough isprobably, there are not many dramatic breakthroughs in science asyou're probably are well aware. And, uh, we're probably are not goingto have major breakthroughs, uh, during my lifetime here in, in curingdiseases, but perhaps we'll add some building blocks to understandingabout, uh, how to approach Alzheimer's disease and perhaps how theimmune system does age and how that might allow, uh, diseases to affectthe elderly that won't affect the younger person whose immune responseis intact. And it's true these small little incremental buildingblocks that we'll be making, uh, having a major impact and perhapshelping mankind. I guess the programs we have that, uh, give direct49:00care to people can be weighed into this in some way, even though wemight not cure diseases, we help families care for them and we helpdiagnose them and we have our programs for the elderly, uh, be itexercise fitness or classes for them or workshops or whatever; I guessthere's some direct benefit there, but, uh, primarily looking at theresearch effort, it's gonna be only through adding small increments toour knowledge base that will probably have an impact.

SMOOT: Let me ask a real cynical devil's advocate sort of question.

Uh, you mentioned the years of research that has been spent on cancer.Some people would say, well, they don't really want to find the answerto cancer too soon. After all, those institutions that have been built50:00up are worth millions and millions of dollars, it provides them withlots of jobs, it gives them something to do, gives an enormously, uh,wonderful lifestyle, et cetera, et cetera. Let's, let's get off insome minute detail over here and not really go after the big questionand, and looking at the big picture and find the answer too soon.Something along the same lines as you might hear from somebody whofound, uh, that water would run an automobile and the automobile andoil industries would not be very happy about that. Uh, what's yourresponse to that sort of a type of question?

MARKESBERY: Well, in my idealism I believe that people working in these

areas would truly love to find a cure instantaneously and take allthe research money that's being poured into cancer and poured intoatherosclerosis, hypertension, diabetes, or some other area untilthat's found out as well. Because, I think, we, we all are, uh,well-meaning in, in research and although each one of us would like51:00to find the breakthrough for cancer or any other disease and say thathey, I've done this and my life is, uh, now has more meaning becauseI have made a major contribution. So, I really, I really don't thinkthat, uh, there's any slowness in the research simply because ofeconomical reasons. I, I haven't, I think the most, everybody in thisfield, uh, although very pragmatic, uh, really would like to find abreakthrough and you hope it would be tomorrow. And you only have tosee one suffering person either as a physician or a lay person and knowwhat a horrible problem cancer is and, uh, I think the good in all ofus would like to see it, see the answer today, and if it's, if it'sa form of vaccine or some magic drug that keeps cells, abnormal cellsfrom dividing, uh, we'd be excited about it and, and, uh, wouldn't52:00mind giving up our research dollars. I mean if somebody could come intomorrow and say, hey, we've got a way of stopping Alzheimer's diseaseand, uh, it's in a form of a pill that costs, uh, two cents each, I'dbe the most excited guy in the world and we'd close up our Alzheimer'sshop and jump into something else, uh, very, very quickly, I was goingto say jump into other problems of the elderly, and I, there's somany of them it is like a big smorgasbord table. Right now you canjust pick and grab what, what you want, what you want to study. AndI think that's the wonderful part about, uh, academic medicine, youhave the freedom to do what you want and study what you want and, uh,give it your best shot, and, uh, hope that you can come out and maybehelp someone. And I, that's why I think it's the most exciting, uh,opportunity in the world and I would do it all over again, uh, the, thesame way, just to be a part of it. I, I really have an immense respect53:00for the field.

SMOOT: Is there anything else you would like to add, uh, to what we have

talked about over the past three sessions, uh, or anything in specificthat you would like to point to regarding a, the development of thehistory of the Medical Center, that you think I have not discussedwith you?

MARKESBERY: No, I think you have done very well. I, I think it's a,

it got off to a very unique start, uh, as far as a state institution.Uh, now it's, uh, it's doing very well, although we're not, youknow, we have areas that we are developing, uh, that make us, uh, setus apart from other state institutions and I think we're, state andmedical centers, and I think we're doing fairly well. I, I happen tobe grateful for my opportunity here and I, I try to be positive aboutthe place and I, I don't think that's inappropriate because I, both my54:00brother and I were given the opportunity to go to school here and, uh,he was in the class behind me here, and I know we're both very gratefulfor all that opportunity and having the state provide us with thatopportunity and giving us both the opportunity to practice medicine inour different ways, uh, and to learn from it and to have a lifestylethat's very exciting. I really don't have, I'm delighted to seesomebody putting this all together. I'm afraid I've given you too muchof my personal philosophy rather than historical part of this, but, uh,I sort of answered them as they came. (laughs)

SMOOT: Well, there is a lot that can be learned from that as well. And

I appreciate your time and your comments very much. On behalf of theMedical Center, the library and myself, thank you.